The objective of our competing renewal application for the University of Chicago Research Training Program in Respiratory Biology is to prepare young scientists to pursue research careers addressing mechanisms and treatment of human disease, with a focus on respiratory pathobiology. The cohesiveness of this interdisciplinary Program stems from the highly collaborative nature of our 43 well-funded faculties in 7 departments at the University of Chicago in 3 areas of concentration: Studies in Airway Biology continue to focus on airway inflammation, ain/vay smooth muscle and epithelial structure and function, B-cell and T-cell activation, and asthma genetics. These complement a new program of Studies in Pulmonary Fibrosis/Luna Transplantation that focuses on cellular and molecular mechanisms of fibrosis and on transplantation immunology. Studies in Critical Illness continue to address subcellular determinants of oxygen sensing and consumption, cellular responses to hypoxia, membrane biology, protection against ischemic injury, and bedside translations to patients with sepsis or cardiopulmonary arrest. During the previous grant period, extremely strong programs in endothelial biology, pulmonary vascular disease, and acute lung injury were added. Complementing all 3 areas are new cross-cutting programs in systems biology draws on creative informatics and genetics tools, in translational medicine to speed improvement in human health, in research ethics to address advances in biotechnology and critical illness, and in nanomedicine to facilitate ultrastructural analyses and develop novel therapeutics. The Program Director is Julian Solway, MD, Prof of Medicine and Pediatrics, with Associate Directors Anne Sperling, PhD (Mentorship) and Steven White, MD (Administration). Christopher Olopade, MD, MPH chairs a Diversity Committee. Internal and External Advisory Committees meet yearly to provide oversight and continuity of review, and an Admissions Committee meets bimonthly to review trainee progress. We request funding for 10 post-doctoral trainees. PhD and MD trainees are enrolled in approximately equal numbers and train together. All fellows perform full-time research for at least 2 years, and MD fellows will not receive clinical training while supported by this Program. Training consists of 4 major components: a Research Project performed under the direct supervision of faculty co-mentors; a Core Curriculum of robust seminar series and courses with additional, tailored formal coursework; Learnina of Survival Skills that includes scientific communication, grant writing, and mentoring, and Multidisciplinarv Research. Prior trainees from this Program have developed successful independent research careers in large proportion. Refinements presented here should further enhance the likelihood for success of future trainees.